Clinical Features

Consists of 2 key elements:
1. Clinical manifestations of urticaria
  - Skin lesions differ from common urticaria
    - Wheals may have a central dark or red appearance
    - Lesions last >24 h
      - Note that large urticarial plaques may need more than a day to resolve and this should not be confused with vasculitis lesions
    - Often resolve with residual hyperpigmentation
    - Typically painful with a burning/stinging sensation
    - Pruritis less common than true urticaria
    - In contrast to above, a series of UV patients showed 60% with lesions lasting <24 h, 80% with pruritic lesions, and 8% with painful/tender lesions
2. Histology demonstrating leukocytoclastic vasculitis (largely involving postcapillary venules)
  - 80% will have positive immunofluorescence for immunoglobulin, complement, or fibrin (not specific for UV and can be seen in SLE)
Often presents with other systemic symptoms:
- Musculoskeletal (arthritis)
- Pulmonary (COPD)
- Renal
- GI
Clinical subtypes may be differentiated by complement levels:
- CH50, C3, C4, C1q
- To conclusively state as normal should be repeated 2-3 times over several months during both active disease and quiescence

Normocomplementemic UV (NUV)

Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS)------

Hypocomplementemic UV (HUV)

Most cases are idiopathic
Can be secondary to:
- Monoclonal gammopathy------
- Neoplasia
- UV light sensitivity
- Repeated cold exposure

Have low complement and UV but otherwise do not meet criteria for HUVS
Most cases due to:
- SLE
- Sjogren's syndrome------
- Serum sickness
- Neoplasia

Other Conditions Associated with UV

Schnitzler's syndrome — monoclonal IgM or IgG gammopathy with intermittent spiking fever, weight loss, bone pain, arthralgias, lymphadenopathy, and nonpruritic urticaria (later may become pruritic); may be due to circulating immune complexes and complement activation, responds to anakinra (IL1R antagonist)
Cryopyrin-associated autoinflammatory syndromes (CAPS)
Cryoglobulinemia, often associated with Hepatitis C

Obtain in patients with compatible clinical and histologic presentation
Complement levels - to conclusively state as normal should be repeated 2-3 times over several months during both active disease and quiescence
- CH50, C3, C4
- C1q
- Anti-C1q antibodies (C1q precipitins) - found in 100% of patients with HUVS
  - May also be found in Felty's syndrome, SLE, Sjogren's, MPGN
CBC with differential
Urinalysis
Chemistries
Hepatitis B and C serologies
ANA, anti-dsDNA, anti-Ro (SS-A), anti-La (SS-B), anti-Smith, anti-RNP, anti-Scl70, anti-Jo
ANCA
RF and anti-CCP antibody
SPEP
Cryoglobulins
Other investigations as appropriate:
- Chest XR, CT
- Skeletal XR in patients with joint pain
- PFTs (to look for COPD)